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Query: UMLS:C0001127 (respiratory acidosis)
 1,501 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The isolated perfused working rat heart preparation has been used to study the effects of respiratory acidosis on myocardial metabolism and contractilly. Hearts were perfused with 5 mM glucose and 10(-2) U/ml of insulin in order to enhance metabolsim of glucose relative to that of fatty acids. After perfusion with Krebs bicarbonate medium at pH 6.6, hearts rapidly ceased performing external work and peak left ventricular pressure fell by 75% after 5 minutes. Oxygen consumption, rate of ATP generation and overall glycolytic flux also declined rapidly. After about 2 minutes of perfusion, the fall of glycolytic flux showed a partial reversal, which was largely accounted for by increased lactate production, so that glucose oxidation decreased further. The reversal of glycoltic flux could be accounted for by partial release of H+ inhibition of phospho-fructokinase by increased tissue levels of adenosine 5'-diphosphate (ADP), adenosine monophosphate (AMP) and P1 and decreased levels of adenosine triphosphate (ATP) and creatine phosphate. The increased proportion of glucose uptake converted to lactate together with an increase of the tissue lactate/pyruvate ratio could be accounted for by inhibition of the malate-aspartate cycle combined with tissue hypoxia. Lactate accumulated in the tissue as a result of a decreased permeability of the plasma membrane to lactate. Decreased oxygen delivery to the myocardium was caused by secondary constriction of the coronary vessels. In further experiments, the coronary flow was regulated by an external pump which delivered fluid at a controlled rate into the aortic cannula above the coronary arteries, and the degree of tissue hypoxia was monitored by measuring changes of pyridine nucleotide reduction state by surface fluorescence techniques. The effects of acidosis uncomplicated by possible hypoxia were compared directly with those produced by ischemic hypoxia. The effects of acidosis under these conditions were similar to those described above, and to those produced by ischemia. From these and other data it is concluded that the effects of ischemia are caused by a lowering of the intracellular pH, which decreases the rate of energy production relative to the rate of energy demand. However, it is suggested that the primary cause of the decreased peak systolic pressure with either acidosis or ischemia is not a result of a defect of energy metabolism, but is due to alteration of the calcium cycle of the heart. Possible causes of irreversible heart failure after prolonged ischemia are discussed.
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PMID:Contribution of tissue acidosis to ischemic injury in the perfused rat heart. 0 93

Tissue oxygen gradients were examined in the saline-perfused rat heart by NADH fluorescence photography. In high flow hypoxia, where the coronary flow was maintained and the arterial oxygen tension was gradually reduced, oxygen extraction was virtually complete before oxygen consumption was significantly diminished. Inadequate oxygen delivery resulted in a well defined pattern of anoxic zones. The anoxic zones were several hundred microns in width, an order of magnitude greater than intercapillary distances. In low flow hypoxia (ischemia), where the arterial oxygen tension remained at its control value and the coronary flow was diminished, anoxic zones also developed, following the same pattern as in high flow hypoxia. However, in ischemia, the anoxic areas developed while the effluent oxygen tesion was significantly greater than zero. Whereas respiratory acidosis between pH 7.3 and 6.9 resulted in vasodilation, below PH 6.8 there was a marked increase in vascular resistance. Anoxic zones appeared despite only a slight change in effluent oxygen tension from the control. In high flow hypoxia, ischemia, and acidosis-induced ischemia, the anoxic zones disappeared when control perfusion conditions were restored. The data demonstrate that tissue oxygen gradients are very steep in the hypoxic state, so that ischemia and hypoxia result in discrete heterogeneous areas of anoxic tissue bounded by sharp areas where the oxygen supply is sufficient to maintain normal mitochondrial oxidative function. In these states in which oxygen delivery is less than oxygen demand, coronary perfusion appears to be regulated at the level of the arterioles rather than the capillaries.
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PMID:Heterogeneity of the hypoxic state in perfused rat heart. 90 8

A 46-year-old man underwent cosmetic facial surgery under general anesthesia. He was ventilated by mask with an oxygen-enriched gas mixture for 4 to 6 h and monitored by pulse oximetry. Despite adequate arterial saturation (SaO2 > 90 percent) throughout the procedure, he remained in a deep coma after termination of anesthesia. Initial arterial blood gas analysis revealed a pH of 6.60 and a PaCO2 of 375 mm Hg. The patient was intubated and placed on mechanical ventilation. As his respiratory acidosis resolved, he regained consciousness quickly and recovered without any neurologic deficits. This case of record extreme hypercapnia and review of the literature demonstrates that survival is possible in acute severe respiratory acidosis as long as tissue anoxia and ischemia are prevented. We discuss the tissue effects of acute hypercapnia and newer aspects of the nature of intracellular pH regulation in critical tissues that afford considerable tolerance to acidosis. The dependence of these mechanisms upon active ion transport underscores the importance of adequate tissue oxygenation and perfusion.
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PMID:Resuscitation from severe acute hypercapnia. Determinants of tolerance and survival. 144 82

The authors sought to determine how hypoperfusion influences acid-base balance in arterial and mixed venous blood. In anesthetized, ventilated pigs (n = 12), we determined hemodynamics, O2 uptake, CO2 output, dead-space ventilation, arterial and mixed venous blood acid-base balances, and lactate concentrations during graded reductions in cardiac output by incremental positive end-expiratory pressure (PEEP, 0-20 cm H2O). Cardiac output decreased from 3.2 +/- 0.2 (mean +/- SEM) to 1.2 +/- 0.1 L/min at 20 cm H2O PEEP. Oxygen delivery declined more than O2 uptake did by 60% +/- 2% and 27% +/- 2%, respectively. The decrease in CO2 output (by 21% +/- 2%) was less than that in O2 uptake. Fractional dead-space ventilation increased. At a slight increase in carbon dioxide tension (PCO2) of 4 +/- 1 mm Hg, pH decreased in arterial blood from 7.54 +/- 0.01 to 7.47 +/- 0.02 mmol/L, and standard bicarbonate decreased from 30.3 +/- 0.5 to 27.5 +/- 0.6 mmol/L. The decrease in standard bicarbonate exceeded the increase in blood lactate concentrations. At a similar decrease in standard bicarbonate, the decrease in pH was larger (P less than 0.005) in mixed venous blood than in arterial blood owing to a larger increase in PCO2 (from 40 +/- 2 to 50 +/- 2 mm Hg, P less than 0.005). The changes were reversed after discontinuing PEEP. The authors conclude that ischemia after incremental PEEP results in tissue metabolic acidosis with superimposed respiratory acidosis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Arterial and mixed venous blood acid-base balance during hypoperfusion with incremental positive end-expiratory pressure in the pig. 195 38

Opinions are still not unanimous about the mechanism behind circulation during external cardiac compression and this leads to uncertainty regarding the correct frequency, force of compression and its duration. Adrenaline and other alpha-stimulators increase blood flow during external cardiac compression and increase survival. Cardiac arrest results in anaerobic metabolism and combined metabolic and respiratory acidosis. On account of relatively low minute volume during external cardiac compression decrease in end-tidal carbon dioxide concentration is observed together with arterial alkalosis on account of hyperventilation and venous acidosis. No communications exist about the favourable effect of administration of bicarbonate during cardiac arrest. On the other hand, several conditions suggest that bicarbonate increases the intracellular acidosis with poorer possibilities for resuscitation with this form of treatment. Ischaemia results inter alia in intracellular accumulation of calcium which initiates potential cell destructive processes. No investigations are available which favour employment of calcium during cardiac arrest. Conversely animal experiments suggest the possibility of favourable effects from calcium-entry blockers. Ischaemia and, in particular, reperfusion release cell and vessel damaging free oxygen redicals. Intensive investigations are being conducted at present about the value of anti-oxidants for cerebral and myocardial protection.
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PMID:[Treatment of cardiac arrest. Recent aspects of cardiopulmonary resuscitation]. 267 53

The conductance of the inward-rectifying K+ current (IK1) in isolated cat ventricular myocytes is decreased by reducing the extracellular Na+ concentration. Using a whole-cell patch-clamp technique, possible mechanisms underlying this Na+ dependence were investigated. These included (a) block of inward K+ current by the Na+ substitute, (b) changes in membrane surface charge associated with removal of extracellular Na+, (c) increases of intracellular Ca2+ due to suppression of Na-Ca exchange, (d) reduction of a Na+-dependent K+ conductance due to a subsequent decrease of intracellular Na+, (e) reduction of IK1 conductance (gK1) associated with reduction of intracellular pH due to suppression of Na-proton exchange. The findings support the hypothesis that the effect of removing Na+ is mediated through a decrease in intracellular pH. These include observations that: (a) reducing internal pH by reducing external pH caused a decrease in gK1, and the conductance changes caused by reducing extracellular pH and removing extracellular Na+ were not additive: (b) the effect of reducing pHo was attenuated by dialyzing with a low pH internal solution; (c) gK1 was reduced by exposure to the Na-proton exchange inhibitor dimethylamiloride, and this effect was absent in the absence of Na+. These findings imply that physiological or pathological processes such as ischemia and metabolic or respiratory acidosis which can produce intracellular acidosis should be expected to affect K+ permeation through the IK1 channel.
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PMID:On the role of sodium ions in the regulation of the inward-rectifying potassium conductance in cat ventricular myocytes. 279 68

Ischemia causes myocardial acidosis and elevation of myocardial CO2 tension (PCO2). We performed the present study to examine whether accumulation of hydrogen ion is a cause or result of accumulation of CO2. The myocardial pH and PCO2 were measured simultaneously in the dog heart, and the concentration of HCO-3 [( HCO-3]) was calculated according to the Henderson-Hasselbalch equation. Ischemia was induced by either partial or complete occlusion of the left anterior descending coronary artery (LAD). After LAD occlusion, the myocardial pH decreased with a marked decrease in [HCO-3], indicating that metabolic acidosis occurred. We ascertained in experiments with blood sample in vitro that an addition of lactic acid into blood decreased both [HCO-3] and pH (metabolic acidosis), whereas an addition of CO2 gas into blood increased [HCO-3] and decreased pH (respiratory acidosis). These findings suggest that ischemic acidosis is not respiratory in nature, but metabolic. The myocardial pH decrease due to ischemia, however, cannot be explained by the tissue lactate accumulation alone, because the decrease of [HCO-3] is far greater than the increase of lactic acid during ischemia.
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PMID:Is ischemia-induced pH decrease of dog myocardium respiratory or metabolic acidosis? 642 24

To investigate the contribution of acidosis to contractile dysfunction during early myocardial ischemia, miniature intramyocardial pH electrodes (0.2 mm tip diam) were used to correlate changes in extracellular pH (pHo) with tension in the isolated arterially perfused rabbit interventricular septum. A number of findings argue against acidosis as the major cause of contractile failure during early ischemia. During hypoxia without glucose present, the rate and pattern of tension decline was very similar to total ischemia, suggesting that a common mechanism is involved. Throughout the initial period in which tension declined by 50%, however, pHo increased in the six of eight preparations during hypoxia without glucose. During hypoxia with glucose present, tension fell less rapidly than during hypoxia without glucose despite a significantly greater fall in pHo in the former case. The maximal rate of relaxation (-dT/dt) was markedly more sensitive to ischemia, hypoxia, or exposure to inhibitors of aerobic metabolism (2,4-dinitrophenol and Na azide) than the maximal rate of force development (+dT/dt). In contrast, +dT/dt and -dT/dt decreased almost symmetrically during exposure to respiratory acidosis. During ischemia, the change in pHo associated with 50% reduction in tension was 0.11 +/- 0.04 units. During respiratory acidosis, this value was 0.45 +/- 0.02 units. From these observations we concluded that acidosis is unlikely to be a major factor in the early decline of tension during ischemia.
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PMID:Role of acidosis in early contractile dysfunction during ischemia: evidence from pHo measurements. 649 57

Double-barreled valinomycin K+-sensitive electrodes and floating microelectrodes were used to monitor extracellular K+ concentration ([K+]o) and intracellular potential, respectively, in the isolated arterially perfused rabbit interventricular septum, under conditions of global ischemia without collateral flow and hypoxia with maintained flow. During ischemia [K+]o reproducibly increased at rates of 0.5-1 mM/min, usually in a triphasic pattern, and was accompanied by shortening of the action potential duration (APD) and an increase in conduction time (CT). Hyperkalemia, equivalent to that occurring during ischemia, in combination with respiratory acidosis (pH 6.2-6.5) and catecholamines reproduced quantitatively the ischemia-induced changes in APD and CT. None of these factors alone produced quantitatively comparable electrophysiological changes. Faster heart rates increased [K+]o accumulation during ischemia and accentuated the changes in APD and CT during ischemia. These findings suggest that local hyperkalemia, intracellular acidosis, and catecholamines release during early ischemia may account for electrophysiological changes predisposing to the development of reentrant arrhythmias.
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PMID:[K+]o accumulation and electrophysiological alterations during early myocardial ischemia. 711 41

We studied the individual and combined effects of extracellular acidosis and increases in extracellular potassium on action potential characteristics and conduction in order to gain a better understanding of the effects of acute ischemia. At each level of potassium between 2.7 and 17 mm, acidosis induced by increasing Pco2 (respiratory acidosis) and by decreasing HCO3- (metabolic acidosis) decreased resting membrane potential, the maximum rate of rise of the action potential upstroke (Vmax), and slowed conduction. Metabolic acidosis consistently and significantly lengthened the steady state action potential duration whereas respiratory acidosis did not. Respiratory acidosis caused changes in resting membrane potential, Vmax, and conduction velocity; which occurred more rapidly and were of greater magnitude than the changes induced by metabolic acidosis. The changes in Vmax induced both types of acidosis were due to a change in the resting membrane potential-Vmax relationship as well as to the changes in the resting membrane potential. The conduction slowing induced by acidosis was greater when potassium was 9 and 13 mM than when potassium was 5.4 mm. Our results suggest that acidosis causes important changes in the electrophysiological properties of ventricular fibers and that many of the known electrophysiological effects of acute ischemia can be mimicked by the combined effects of extracellular acidosis and an increase in extracellular potassium.
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PMID:Interaction of acidosis and increased extracellular potassium on action potential characteristics and conduction in guinea pig ventricular muscle. 713 80


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